Cargando…

Evidence that two instead of one defective interfering RNA in influenza A virus-derived defective interfering particles (DIPs) does not enhance antiviral activity

Influenza A virus (IAV) infection constitutes a significant health threat. Defective interfering particles (DIPs) can arise during IAV infection and inhibit spread of wild type (WT) IAV. DIPs harbor defective RNA segments, termed DI RNAs, that usually contain internal deletions and interfere with re...

Descripción completa

Detalles Bibliográficos
Autores principales: Bdeir, Najat, Arora, Prerna, Gärtner, Sabine, Pöhlmann, Stefan, Winkler, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516915/
https://www.ncbi.nlm.nih.gov/pubmed/34650149
http://dx.doi.org/10.1038/s41598-021-99691-1
_version_ 1784583898509869056
author Bdeir, Najat
Arora, Prerna
Gärtner, Sabine
Pöhlmann, Stefan
Winkler, Michael
author_facet Bdeir, Najat
Arora, Prerna
Gärtner, Sabine
Pöhlmann, Stefan
Winkler, Michael
author_sort Bdeir, Najat
collection PubMed
description Influenza A virus (IAV) infection constitutes a significant health threat. Defective interfering particles (DIPs) can arise during IAV infection and inhibit spread of wild type (WT) IAV. DIPs harbor defective RNA segments, termed DI RNAs, that usually contain internal deletions and interfere with replication of WT viral RNA segments. Here, we asked whether DIPs harboring two instead of one DI RNA exert increased antiviral activity. For this, we focused on DI RNAs derived from segments 1 and 3, which encode the polymerase subunits PB2 and PA, respectively. We demonstrate the successful production of DIPs harboring deletions in segments 1 and/or 3, using cell lines that co-express PB2 and PA. Further, we demonstrate that DIPs harboring two instead of one DI RNA do not exhibit increased ability to inhibit replication of a WT RNA segment. Similarly, the presence of two DI RNAs did not augment the induction of the interferon-stimulated gene MxA and the inhibition of IAV infection. Collectively, our findings suggest that the presence of multiple DI RNAs derived from genomic segments encoding polymerase subunits might not result in increased antiviral activity.
format Online
Article
Text
id pubmed-8516915
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-85169152021-10-15 Evidence that two instead of one defective interfering RNA in influenza A virus-derived defective interfering particles (DIPs) does not enhance antiviral activity Bdeir, Najat Arora, Prerna Gärtner, Sabine Pöhlmann, Stefan Winkler, Michael Sci Rep Article Influenza A virus (IAV) infection constitutes a significant health threat. Defective interfering particles (DIPs) can arise during IAV infection and inhibit spread of wild type (WT) IAV. DIPs harbor defective RNA segments, termed DI RNAs, that usually contain internal deletions and interfere with replication of WT viral RNA segments. Here, we asked whether DIPs harboring two instead of one DI RNA exert increased antiviral activity. For this, we focused on DI RNAs derived from segments 1 and 3, which encode the polymerase subunits PB2 and PA, respectively. We demonstrate the successful production of DIPs harboring deletions in segments 1 and/or 3, using cell lines that co-express PB2 and PA. Further, we demonstrate that DIPs harboring two instead of one DI RNA do not exhibit increased ability to inhibit replication of a WT RNA segment. Similarly, the presence of two DI RNAs did not augment the induction of the interferon-stimulated gene MxA and the inhibition of IAV infection. Collectively, our findings suggest that the presence of multiple DI RNAs derived from genomic segments encoding polymerase subunits might not result in increased antiviral activity. Nature Publishing Group UK 2021-10-14 /pmc/articles/PMC8516915/ /pubmed/34650149 http://dx.doi.org/10.1038/s41598-021-99691-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bdeir, Najat
Arora, Prerna
Gärtner, Sabine
Pöhlmann, Stefan
Winkler, Michael
Evidence that two instead of one defective interfering RNA in influenza A virus-derived defective interfering particles (DIPs) does not enhance antiviral activity
title Evidence that two instead of one defective interfering RNA in influenza A virus-derived defective interfering particles (DIPs) does not enhance antiviral activity
title_full Evidence that two instead of one defective interfering RNA in influenza A virus-derived defective interfering particles (DIPs) does not enhance antiviral activity
title_fullStr Evidence that two instead of one defective interfering RNA in influenza A virus-derived defective interfering particles (DIPs) does not enhance antiviral activity
title_full_unstemmed Evidence that two instead of one defective interfering RNA in influenza A virus-derived defective interfering particles (DIPs) does not enhance antiviral activity
title_short Evidence that two instead of one defective interfering RNA in influenza A virus-derived defective interfering particles (DIPs) does not enhance antiviral activity
title_sort evidence that two instead of one defective interfering rna in influenza a virus-derived defective interfering particles (dips) does not enhance antiviral activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516915/
https://www.ncbi.nlm.nih.gov/pubmed/34650149
http://dx.doi.org/10.1038/s41598-021-99691-1
work_keys_str_mv AT bdeirnajat evidencethattwoinsteadofonedefectiveinterferingrnaininfluenzaavirusderiveddefectiveinterferingparticlesdipsdoesnotenhanceantiviralactivity
AT aroraprerna evidencethattwoinsteadofonedefectiveinterferingrnaininfluenzaavirusderiveddefectiveinterferingparticlesdipsdoesnotenhanceantiviralactivity
AT gartnersabine evidencethattwoinsteadofonedefectiveinterferingrnaininfluenzaavirusderiveddefectiveinterferingparticlesdipsdoesnotenhanceantiviralactivity
AT pohlmannstefan evidencethattwoinsteadofonedefectiveinterferingrnaininfluenzaavirusderiveddefectiveinterferingparticlesdipsdoesnotenhanceantiviralactivity
AT winklermichael evidencethattwoinsteadofonedefectiveinterferingrnaininfluenzaavirusderiveddefectiveinterferingparticlesdipsdoesnotenhanceantiviralactivity